The interaction of IL-2 with its receptor is critical not only to induce proliferation but is also required to allow activated T cells to complete the G1 phase of the cell cycle. The signal(s) generated through the IL- 2/IL-2R interaction during the G1 phase upregulates the expression of certain critical T-cell activation genes and dictates the expression of cdc2. Disruption of the IL-2/IL-2R interaction blocks cells in late G1 and cell death occurs within 24 hours. The interaction of IL-2 with high affinity IL-2R that induces the entry of activated murine T-cells into S phase and initiates DNA synthesis is associated with an increase in the level of tyrosine phosphorylation of a single 97 kDa protein and a rapid transient increase in the kinase activity of p561ck.